(F) Mendelian Disorders Flashcards
Mendelian Disorders
Which is not true:
A. Each person carries 5-8 deleterious genes
B. Mutation in single gene only with minimal effects
C. Majority of the disorders are familial
D. Other Mendelian disorders are de novo
E. NOTA
B (large effects)
MENDELIAN DISORDERS
Three patterns of transmittance:
Autosomal dominant
Autosomal recessive
X-linked
Almost all sex-linked are recessive
TOF. Penetrance is expressed in
mathematical terms.
T
TOF. 50% penetrance indicates that 100% of
those who carry the gene express the
trait.
F (both 50%)
1:1
TOF. If a trait is seen in all individuals carrying the mutant gene but is expressed differently among individuals, the phenomenon is called chosen expressivity.
F (variable expressivity)
Identify pattern
Origin: Do not affect parents, may manifest in sibling
AR
Identify pattern
Some are de novo in gametes
AD
Identify pattern
Clinical: Modified by variation in PENETRANCE and EXPRESSIVITY; M=F
AD
Which is not true about X-Linked
A. All daughters are carriers
B. Almost all are recessive
C. Expressed in MALES
D. It’s onset is depends on the disease
E. NOTA
E
X-Linked
Type of Protein
Enzyme or Structural proteins
AD
Type of Protein
Non-enzyme proteins;
membrane receptors and Structural proteins
AR
Type of Protein
Enzyme proteins
Identify pattern
More uniform expression, commonly with complete penetrance
AR
TOF. The age of onset in AD is delayed while AR is early.
T
AD, AR or X-linked
Deletion
All
AD, AR or X-linked
non-functional
AR
AD, AR or X-linked
missense mutation; LOF, GOF
AD
AD, AR or X-linked
insertions, non-sense mutations
X
AD, AR or X-linked
They only manifest when homozygous.
AR
TOF. In Autosomal Dominant disorders, only ONE ALLELE needs to have the mutation for the autosomal dominant disorder to manifest.
T
It only takes one allele.
AD, AR or X-linked
→ Duchene Muscular Dystrophy
X-Linked
AD, AR or X-linked
Hemophilia B
X
AD, AR or X-linked
Ehlers-Danlos
AD
They can be transmitted through AR fashion, or sex as a sex-linked disorder.
AD, AR or X-linked
Marfan syndrome
AD
AD, AR or X-linked
Lysosomal Storage Disease
AR
AD, AR or X-linked
Mucopolysaccharidosis
AR
AD, AR or X-linked
Familial Hypercholesterolemia
AD
AD, AR or X-linked
Cystic fibrosis
AR
AD, AR or X-linked
Hereditary Spherocytosis
AD
AD, AR or X-linked
Glycogenosis
AR
Marfan Syndrome
Except:
A. FBN2 on 5q23.31
B. FBNI on 15q21.1
C. fibrillin I protein
D. COL5A1
E. NOTA
D
Marfan Syndrome
The Fibrilin I protein crated from the FBNI gene provides skeleton on which trophoelastin
is deposited to form?
Elastic fibers
Marfan Syndrome
Appearance except:
A. Long extremities
B. Dolichocephaly
C. Prominent supraorbital ridges
D. Pectus excavatum
E. NOTA
E
Marfan Syndrome
Appearance except:
A. Spinal deformity
B. Pigeon-breast deformity
C. Bilateral subluxation
D. Single joints
E. NOTA
D (double joints)
Marfan Syndrome
What do you call when when the left the ventricle contracts, a portion of the blood goes back to the left atrium?
mitral valve prolapse
Marfan Syndrome
TOF. Aneurysm of ascending aorta can result to competence of the aortic valve.
F (incompetence)
MArfann Syndrome
The incompetence if the aortic valve is caused by?
aneurysm of the ascending aorta
Marfan Syndrome
Mitral valve prolapse creates a volume overload in what part of the heart?
Left ventricle
Marfan Syndrome
increase in the size of individual muscle fibers in the heart is a condition called?
hypertrophy
continuous process of overload, this can result to Heart Failure (HF)
Abraham Lincoln has a condition called?
Marfan Syndrome
Marfan Syndrome
Diagnosis, except:
A. Lens dislocation
B. Ectopia lentis
C. Echocardiography
D. Clinical
E. NOTA
E
Ehlers-Danlos Syndrome
TOF. Group of clinically and genetically heterogenous disorders.
T
Ehlers-Danlos Syndrome
Defect in synthesis of?
fibrillar collagen
EDS
The defect in synthesis of firbrillar collagen is caused by what pattern of inheritance?
AD
Ehlers-Danlos Syndrome
what gene is affected for classical EDS,
Type I and II
COL5A1 and COL5A2
Ehlers-Danlos Syndrome
COL1A1 and COL1A2
arthrochalasia, type VIIa, b
Syndrome
may be caused by mutations involving
structural proteins or enzymes
EDS
Ehlers-Danlos Syndrome
Common manifestations, except:
A. hypermobility
B. dark skinned
C. hyperextensibility
D. NOTA
B
Ehlers-Danlos Syndrome
ocular fragility can cause
corneal rupture and retinal detachment (Kyphoscoliosis variant)
EDS Variant
the skin is fragile, it is prone to trauma and injury, particularly in patients with?
dermatosparaxis variant
EDS Variant
Colon and arterial rupture are seen in individuals with?
vascular variant
Ehlers-Danlos Syndrome
TOF. in classical variant, they can have the diaphragmatic hernia
T
Ehlers-Danlos Syndrome
The diaphragm, which separates the thoracic
cavity from the abdominal cavity can become
weak and so we know that the esophagus
traverses the diaphragm before it comes to
stomach. That segment can be pulled up into the
thoracic cavity, which is called?
diaphragmatic hernia
Ehlers-Danlos Syndrome
TOF. A portion of the stomach can GO UP into the thoracic cavity.
T
vewy flexible sya, kaya p’wede sila makita sa mga circus
Most common lethal genetic diseases
affecting Caucasians
Mucoviscidosis or Cystic Fibrosis
CYSTIC FIBROSIS
This regulates Cl channel, K channel, ENaC,
gap junction channel and cellular processes involved in ATP transport and mucous secretion.
A. Cystic fibrosis transmembrane conductance regulator gene
B. 7q31.2
C. Both
C
CYSTIC FIBROSIS
Normally CFTR inhibits?
ENaC (epithelial sodium channel) in glands
Mutation in the CFTR, will increase the uptake of?
sodium
from the lumen of the pulmonary and GI tract
CYSTIC FIBROSIS
A person with this condition will have a defective ciliary action, the individual will have a hard time to remove the organism in a tracheobronchial tree. This can grow and cause?
infection
Mendelian Disorder
presents with recurrent pulmonary
infection
mucoviscidosis or cystic fibrosis
Mendelian Disorder
hypertonic (high Cl and Na) sweat “salty sweat”
Cystic Fibrosis
this is due to the ENaC having a decreased activity with CFTR mutatio
Cystic Fibrosis
This is a mediated bicarbonate transport, with
mutation tissues that will secrete acidic fluid. Forming a mucin precipitation, plugging of ducts and increase the binding of bacteria to plugs.
CFTR
Mucoviscidosis
Manifests before birth:
Meconium Ileus
Cystic Fibrosis
The absence of that peristalsis that move the food in the GIT is called
Ileus
Cystic Fibrosis
At what developmental stage are viscous secretions
and recurrent pulmonary infection is most serious?
Childhood/adolescence
Cystic Fibrosis
Pancreatic insufficiency (80-90%) can cause?
steatorrhea, malnutrition
fat is not absorbed properly so these undigested fats are expelled together with stools which is called steatorrhea. This, eventually, can lead to malnutrition.
Hereditary deficiency of one of the enzymes involved in glycogen synthesis or degradation
GLYCOGENOSIS
GLYCOGENOSIS
3 subgroups
o Hepatic
o Myopathic
o Glycogen
GLYCOGENOSIS
TOF. Enzymatic defects does not dictate the organ of involvement (distribution)
F
GLYCONGENOSIS
This subgroup is a storage disease associated with deficiency of alpha-glucosidase or acid maltase and lack of debranching enzymes
Glycogen
GLYCOGENOSIS
Muscle phosphofructokinase deficiency
A. MYOPATHIC FORMS
B. HEPATIC FORMS
C. Acid Maltase and Lack of Debranching Enzymes
A
Type VII
Von Gierke/ Type I (Glucose 6 phosphatase
deficiency)
A. MYOPATHIC FORMS
B. HEPATIC FORMS
C. Acid Maltase and Lack of Debranching Enzymes
B
McArdle Disease/type V (Muscle phosphorylase deficiency)
A. MYOPATHIC FORMS
B. HEPATIC FORMS
C. Acid Maltase and Lack of Debranching Enzymes
A
Lysosomal storage of glycogen in all organs
A. MYOPATHIC FORMS
B. HEPATIC FORMS
C. Acid Maltase and Lack of Debranching Enzymes
C
Acid Maltase and Lack of Debranching Enzymes
most prominent feature
Cardiomegaly
enlargement of the heart
They present with enlargement of liver, hepatomegaly, and decreased glucose in blood, hypoglycemia.
A. MYOPATHIC FORMS
B. HEPATIC FORMS
C. Acid Maltase and Lack of Debranching Enzymes
B
DUCHENE MUSCULAR DYSTROPHY
Except:
A. 2/3 de novo, 1/3 familial
B. Deletion
C. Xp21
D. NOTA
A (1/3 de novo and 2/3 familial)
DUCHENE MUSCULAR DYSTROPHY
Forms an interface between intracellular contractile protein and extracellular matrix
Dystrophin
DUCHENE MUSCULAR DYSTROPHY
TOF. Females are carriers, asymptomatic, increase in creatine kinase in the blood.
T
DUCHENE MUSCULAR DYSTROPHY
TOF. Females manifest at 5 y.o, wheelchair dependent at 10-12
F (males)
DUCHENE MUSCULAR DYSTROPHY
Male and female patients who survive until
adulthood are at risk of having dilated?
cardiomyopathy
DUCHENE MUSCULAR DYSTROPHY
TOF. Normal at Birth.
T
DUCHENE MUSCULAR DYSTROPHY
TOF. Delayed walking due to muscle weakness
T
Pelvic girdle muscles are the first to weaken
DUCHENE MUSCULAR DYSTROPHY
Feature, except:
A. Increase fiber size
B. Pseudohypertrophy of leg muscles
C. Pulmonary failure
D. NOTA
D
DUCHENE MUSCULAR DYSTROPHY
Disease that is closely associated
Becker Muscular Dystrophy
Identify Disorder
Diminished Dystrophin; Mutation causes synthesis of abnormal, smaller protein
Becker Muscular Dystrophy
Becker Muscular Dystrophy
Onset
late childhood or adolescence
Becker Muscular Dystrophy
TOF. They have normal lifespan
compared with Duchene Muscular Dystrophy.
T
Second leading cause of mental retardation
and is the primary cause of inherited mental
retardation
FRAGILE X SYNDROME
FRAGILE X SYNDROME
TOF. 1:1550 for affected males and 1:8000 for affected females
T
FRAGILE X SYNDROME
Incorrect:
A. trinucleotide repeat
(CCC) sequence
B. FMR-1gene
C. detectable at molecular level
A
FRAGILE X SYNDROME
A pre-mutatation has how many repeats?
55-200
A full mutatation has how many repeats?
200-4000 repeats
FRAGILE X SYNDROME
Symptoms, except:
A. Long face with macrognathia
B. High arched palate
C. Micro-orchidism
D. Hyperextensible joints
E. NOTA
C (Macro - big balls)
+ MVP, everted ears and mentally retarded
FRAGILE X SYNDROME
TOF. Carrier males are 20% cytologically and clinically NORMAL. They may transmit the disease to all his daughters and to affected grandchildren thus also known as “transmitting males.”
T
FRAGILE X SYNDROME
TOF. 10% of carrier females are affected and are mentally retarded
F (50)
FRAGILE X SYNDROME
TOF.
Brothers of transmitting males are at 40% risk of
having mental retardation
F (9% risk while grandsons of
transmitting males have 40% risk)
Fragile X Syndrome
What do you call when the grandson of transmitting males have a high risk.
positional risk/Sherman paradox
Fragile X Syndrome
TOF. Clinical features gets lessen with each generation
F
